IDDF2019-ABS-0294 HSF2 promote the mucosal repair in ulcerative colitis by inhibiting pro-inflammatory cytokine and promoting TGF-β Expression

Abstract

Background In our previous study, we found that fecal heat shock transcription factor 2 (HSF2) concentration may be an evaluation index for predicting the mucosal healing of Ulcerative Colitis (UC). So this study is aiming to explore the mechanism of HSF2 in the mucosal repair of UC. Methods The DAI, colon damage score and histopathology score were recorded in DSS induced colitis. The transcription and expression level of HSF2 and TGF-β in the mice colon tissue were detected by PCR and immunohistochemistry. HSF2 levels in HT-29 cells was manipulated by RNA interference and plasmids transfection. The concentrations of IL-1β, TNF-α and TGF-β in cells supernatant were detected by ELISA after induced by LPS. The phosphorylation level of ERK, P38, JNK and Smad2/3 were detected by Western Blot. Results The DAI, colon damage and pathology score of methylprednisolone(MP)treatment group were lower than DSS model group (figure 1). The transcription and expression of HSF2 and TGF-β in colon mucosal tissue were increased and decreased synchronously in DSS model group and MP treatment group(figure 2). The phosphorylation level of ERK, P38 and JNK increased significantly in HSF2 siRNA compared with the negative control group. The concentrations of IL-1β and TNF- α in the supernatant of HT-29 cells increased in HSF2 siRNA group. On the contrary, the phosphorylation level of ERK, P38 and JNK decreased significantly in HSF2-FLAG plasmid transfection compared with the Blank Vector group. The concentrations of IL-1β and TNF- α in the supernatant of HT-29 cells reduced (figure 3, figure 4). The phosphorylation level of Smad2/3 decreased in HSF2 siRNA compared with the negative control group. The concentrations of TGF-β in the supernatant of HT-29 cells reduced in HSF2 siRNA group. On the contrary, the phosphorylation level of Smad2/3 increased significantly in HSF2-FLAG plasmid transfection compared with the Blank Vector group. The concentrations of TGF-β in the supernatant of HT-29 cells increased (Figure 4). Conclusions HSF2 can promote the mucosal repair of ulcerative colitis by inhibiting the inflammatory response and promoting mucosal repair factor expression.